2025PhysiologyOpen access

Beyond Clathrin: Decoding the Mechanism of Ultrafast Endocytosis

Yuuta Imoto, Shigeki Watanabe

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Abstract

Endocytosis in nonneuronal cells requires gradual recruitment of proteins to endocytic sites for inducing membrane curvature and forming scaffolds around the neck of endocytic pits. This recruitment process is thought to be rate-limiting, requiring tens of seconds. In contrast, a form of endocytosis in neurons called ultrafast endocytosis is much faster, requiring only 100 ms. In this review, we compare the mechanisms of protein recruitment during clathrin-mediated endocytosis in nonneuronal cells and ultrafast endocytosis in neurons and discuss how endocytosis can complete within 100 ms. We then discuss the potential clinical relevance of this endocytic pathway.

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Endocytosis in nonneuronal cells requires gradual recruitment of proteins to endocytic sites for inducing membrane curvature and forming scaffolds around the neck of endocytic pits. This recruitment process is thought to be rate-limiting, requiring tens of seconds. In contrast, a form of endocytosis in neurons called ultrafast endocytosis is much faster, requiring only 100 ms. In this review, we compare the mechanisms of protein recruitment during clathrin-mediated endocytosis in nonneuronal cells and ultrafast endocytosis in neurons and discuss how endocytosis can complete within 100 ms. We then discuss the potential clinical relevance of this endocytic pathway.

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Available abstract

Endocytosis in nonneuronal cells requires gradual recruitment of proteins to endocytic sites for inducing membrane curvature and forming scaffolds around the neck of endocytic pits. This recruitment process is thought to be rate-limiting, requiring tens of seconds. In contrast, a form of endocytosis in neurons called ultrafast endocytosis is much faster, requiring only 100 ms. In this review, we compare the mechanisms of protein recruitment during clathrin-mediated endocytosis in nonneuronal cells and ultrafast endocytosis in neurons and discuss how endocytosis can complete within 100 ms. We then discuss the potential clinical relevance of this endocytic pathway.

Key concepts: Endocytosis, Endocytic cycle, Bulk endocytosis, Cell biology, Exocytosis, Clathrin, Amphiphysin, Receptor-mediated endocytosis

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